Drug-induced cardiovascular responding appears to be a common factor among abused drugs that may be linked to psychomotor stimulant activation and increased mesolimbic dopamine levels. Therefore, the pattern of cardiovascular responses to abused drugs may reflect their reward value. We measured heart rate (HR) and vagal tone index (V) before, 60 and 120 min after double-blind administration of low and high dosages of smoked marijuana, or oral alcohol, hydromorphone, pentobarbital, and d-amphetamine. There were two triple-dummy (i.e., smoke, drink, and capsule) placebo sessions. The 12 sessions were in randomized order on approx. alternate days. The subjects were 9 male poly-drug abusers who were residential volunteers. V is a well-validated measure of parasympathetic inhibition of the heart that quantifies respiratory sinus arrhythmia using time series analysis, i.e., beat-to-beat variability in HR that is entrained with respiration. Marijuana, alcohol, and pentobarbital increased HR and decreased V relative to placebo in a dose-dependent manner; these results replicate our previous findings with marijuana and alcohol. D-amphetamine increased HR relative to placebo only at the low dose; it appeared to fail to increase HR at the high dose because of baroreceptor mechanisms associated with blood pressure increases. Hydromorphone had no effect on HR or V at 60 or 120 min after drug ingestion. We have shown that HR increases and V decreases occur immediately after opiate administration, and are well compensated by 60 or 120 min. These results suggest some commonality in the cardiovascular responses to various abused drugs, and may reflect the common excitatory aspects of these drugs. However, cardiovascular responses during the rising blood drug curves may better illustrate this pattern because they occur before compensatory mechanisms develop.